This application claims the priority of German Application 199 32 477.8, filed Jul. 12, 1999, the disclosures of which are expressly incorporated by reference herein.
The present invention relates to a process and an apparatus for measuring density fluctuations caused by pulsed irradiation on a material, particularly biological tissue, in the case of which a measuring signal is acoustically or optically detected, particularly for an apparatus for the photocoagulation of specific points on the ocular fundus and here particularly of pigmented tissue.
It is known to cause changes in a targeted manner on the surface or in the interior of materials by the irradiation of the materials, particularly by laser irradiation. In material processing or in the medical field, this results in a therapeutically effective irradiation of tissue. Corresponding processes and apparatuses are described, for example, in DE 44 00 674 C2; DE 39 35 528 A1 DE 43 00 378 A1 U.S. Pat. No. 4,543,486; A. Tam: xe2x80x9cApplications of Photoacoustic Sensing Techniquesxe2x80x9d, Rev. Mod. Phys., Vol. 58, 381-431 (1986); C. P. Lin, M. W. Kelly: xe2x80x9cCavitations and Acoustic Emission around Laser-Heated Microparticlesxe2x80x9d, Appl. Phys. Lett., Vol 72, 1-3 (1998); and A. A. Oraevsky, S. L. Jacques, F. K. Tittel: xe2x80x9cMeasurement of Tissue Optical Properties by Time-Resolved Detection of Laser-Induced Transient Stressxe2x80x9d, Appl. Optics, Vol. 36, 402-415 (1997).
It is known therefrom to carry out a differentiation of materials by the detection of the mechanical shock waves and acoustic pulses generated during the irradiation step. In the known processes and apparatuses, information concerning characteristics of the material, such as the absorption, the thermal coefficient of expansion and the ablation threshold can be obtained by the opto-acoustic effect.
An object of the present invention is to detect a change of the material caused specifically by the irradiation.
This object has been achieved according to the present invention by providing that at least one of a change of intensity and time slope of a measuring signal occurring during the irradiation of a specific material point, and removing a linear thermo-elastic signal fraction from the measuring signal, by providing that the analyzing device has a separating device operable to separate a thermo-elastic signal fraction from the measuring signal, a measuring device operable to detect intensity and time slope of the measuring signal freed of a thermo-elastic signal fraction, and a detector device operable to detect a change of at least one of the intensity and the time slope of the measuring signal. Furthermore, a use of the apparatus is taught for measuring changes at one or several specific points of a biological tissue, particularly on the fundus of the eye during the irradiation. In addition, the present invention provides an apparatus for the phototherapy, e.g., photocoagulation, of specific points on the ocular fundus, particularly of pigmented tissue.
The acoustic or optical signal caused by the specific change of the material as a result of the irradiation is separated from the thermo-elastic signal which contains only information concerning characteristics of the material. The thermo-elastic signal increases approximately linearly with the applied energy or power, without any change of the time slope of the curve. The change of the material caused specifically by the irradiation results in a change of the intensity and/or of the time slope of the measuring signal.
As a result of the present invention, a control of the influencing or changing of the material by way of the irradiation can be advantageously achieved therefrom by evaluating the acoustically or optically obtained measuring signals, which, in addition to the thermo-elastic expansion, are generated by occurrences, such as chemical reactions, ablation, phase transitions, plasma formation, etc. In addition, the detection of occurrences can also be achieved in the interior of the material to be processed, particularly biological tissue on the fundus of the eye, which is often not optically accessible.
An exact dosimetry of the irradiation is achieved by the present invention with respect to the energy, the power, the time slope and the spatial distribution for achieving the desired effect. This is required particularly in the medical field in the case of a therapeutically effective irradiation of biological tissue. Mainly, with the present invention, an individual dosimetry can be achieved before or during the irradiation, which is necessary particularly in the field of medicine because of the variation of the characteristics of tissue. Such an individual dosimetry for regulating and controlling the laser parameters is desirable, for example, during the coagulation of the ocular fundus. This will be explained in detail in the following by way means of the example of the selective coagulation of the retinal pigment epithelium (RPE).
A number of diseases of the eye can be treated by a coagulation of the RPE. The RPE is a single-cell layer of highly pigmented cells which is situated between the photoreceptors and the vessels to be supplied. Although the strong absorption of the RPE permits a selective depositing of the light energy in this cell layer, as a result of the heat conduction, adjoining cell layers (such as photoreceptors), which do not contribute to a therapeutic success, may also be damaged during the photocoagulation. The propagation of the heat can be prevented by using brief laser exposures. This limits thermal damages of the photocoagulation to the RPE and prevents a loss of vision, so that a selective coagulation of the RPE becomes possible. For increasing the therapeutic range of the selective photocoagulation, multiple pulses are used. Currently, pulse series of 500 pulses with a pulse length of 3 xcexcs are used in clinical studies.
As a function of the apportionment of the laser irradiation, the temperature on the surface of the absorbing melanin granules may become so high that locally there is an evaporation of water and the formation of rapidly expanding gas bubbles which may also destroy cells and tissue. This mechanism is also capable of destroying pigmented cells with few side effects if the pulse energy is situated close to the energy threshold for the bubble formation. These two mechanisms, specifically thermal damages as a result of the denaturing of important biomolecules and thermomechanical damages by bubble formation, which play a varying role at different pulse lengths and pulse numbers, can therefore be used for a selective destruction of the RPE.
For controlling the mechanism and the range of the damage, a dosimetry is advantageous with respect to the pulse energy. Since the transparency of the optical media of the eye and the pigmentation of the RPE varies considerably from one patient to the next, an avoidance of damages to the photoreceptors is permitted as a result of the invention. In contrast to the conventional coagulation, the selective effects on the RPE are not directly visible for the physician because of their spatial boundaries. An advantageous simple non-invasive procedure therefore controls the laser during the coagulation, or previously determines the required laser pulse energy by a test coagulation in the critical range.